A Genetic Clue to Why Autism Affects Boys More

By Alice Park – Wed May 20, 6:20 am ET

Among the many mysteries that befuddle autism researchers: why the disorder affects boys four times more often than girls. But in new findings reported online today by the journal Molecular Psychiatry, researchers say they have found a genetic clue that may help explain the disparity.

The newly discovered autism-risk gene, identified by authors as CACNA1G, is more common in boys than in girls (why that's so is still not clear), and the authors suggest it plays a role in boys' increased risk of the developmental disorder. CACNA1G, which sits on chromosome 17, amid other genes that have been previously linked to autism, is responsible for regulating the flow of calcium into and out of cells. Nerve cells in the brain rely on calcium to become activated, and research suggests that imbalances in the mineral can result in the overstimulation of neural connections and create developmental problems, such as autism and even epilepsy, which is also a common feature of autism. (See six tips for traveling with an autistic child.)

"Our current theories about autism suggest that the disorder is related to overexcitability at nerve endings," says Geri Dawson, chief science officer of Autism Speaks, an advocacy group that provided the genetic data used by the study's authors. "It's interesting to see that the gene they identified appears to modulate excitability of neurons."

For the new study, researchers at the University of California, Los Angeles (UCLA), combed the genetic database of the Autism Genetic Resource Exchange (AGRE), a resource of DNA from 2,000 families with at least one autistic child. The scientists focused on the more than 1,000 genetic samples of families in which at least one son was affected by the disorder, prompted by the results of an earlier study using the same database, which identified a rich autism-related genetic region on chromosome 17 that contained genetic variants more common in boys than in girls. While nearly 40% of the general population has the most common form of CACNA1G, one variant of the gene was more prevalent in autistic boys, researchers found. "There is a strong genetic signal in this region," says Dr. Daniel Geschwind, director of UCLA's Center for Autism Research and Treatment and one of the study's co-authors. "But this gene doesn't explain all of that signal or even half of it. What that means is that there are many more genes in this region contributing to autism." (See pictures of inside a school for autistic children.)

That's not surprising for a disorder as complex as autism - actually, a spectrum of developmental disorders involving impairment in language, social behavior and certain physical behaviors - with symptoms that range widely in number and severity. So far, studies have linked a handful of genes, all of which play a role in the way nerve cells connect and communicate, with autism spectrum disorders. It's likely not only that a large number of genes contribute to the disorder, but also that a different combination of genes - as well as unique interactions between genes and environment - are responsible for each individual case of autism.

So it's certainly a daunting challenge to begin teasing out the individual genes that may contribute to autism, as the UCLA team has with CACNA1G, but databases like AGRE make the job slightly easier. The next step will be to try to use known autism genes to help develop screening tools or early interventions. "We are going to have a much better understanding of the causes of autism over the next five to 10 years," says Dawson. "We're in a period of great discovery."

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Research suggests children can recover from autism

By LINDSEY TANNER, AP Medical Writer Lindsey Tanner, Ap Medical Writer – Fri May 8, 5:24 pm ET

CHICAGO – Leo Lytel was diagnosed with autism as a toddler. But by age 9 he had overcome the disorder. His progress is part of a growing body of research that suggests at least 10 percent of children with autism can "recover" from it — most of them after undergoing years of intensive behavioral therapy.

Skeptics question the phenomenon, but University of Connecticut psychology professor Deborah Fein is among those convinced it's real.

She presented research this week at an autism conference in Chicago that included 20 children who, according to rigorous analysis, got a correct diagnosis but years later were no longer considered autistic.

Among them was Leo, a boy in Washington, D.C., who once made no eye contact, who echoed words said to him and often spun around in circles — all classic autism symptoms. Now he is an articulate, social third-grader. His mother, Jayne Lytel, says his teachers call Leo a leader.

The study, funded by the National Institute of Mental Health, involves children ages 9 to 18.

Autism researcher Geraldine Dawson, chief science officer of the advocacy group Autism Speaks, called Fein's research a breakthrough.

"Even though a number of us out in the clinical field have seen kids who appear to recover," it has never been documented as thoroughly as Fein's work, Dawson said.

"We're at a very early stage in terms of understanding" the phenomenon, Dawson said.

Previous studies have suggested between 3 percent and 25 percent of autistic kids recover. Fein says her studies have shown the range is 10 percent to 20 percent.

But even after lots of therapy — often carefully designed educational and social activities with rewards — most autistic children remain autistic.

Recovery is "not a realistic expectation for the majority of kids," but parents should know it can happen, Fein said.

Doubters say "either they really weren't autistic to begin with ... or they're still socially odd and obsessive, but they don't exactly meet criteria" for autism, she said.

Fein said the children in her study "really were" autistic and now they're "really not."

University of Michigan autism expert Catherine Lord said she also has seen autistic patients who recover. Most had parents who spent long hours working with them on behavior improvement.

But, Lord added, "I don't think we can predict who this will happen for." And she does not think it's possible to make it happen.

The children in Fein's study, which is still ongoing, were diagnosed by an autism specialist before age 5 but no longer meet diagnostic criteria for autism. The initial diagnoses were verified through early medical records.

Because the phenomenon is so rare, Fein is still seeking children to help bolster evidence on what traits formerly autistic kids may have in common. Her team is also comparing these children with autistic and non-autistic kids.

So far, the "recovered" kids "are turning out very normal" on neuropsychological exams and verbal and nonverbal tests, she said.

The researchers are also doing imaging tests to see if the recovered kids' brains look more like those of autistic or nonautistic children. Autistic children's brains tend to be slightly larger than normal.

Imaging scans also are being done to examine brain function in formerly autistic kids. Researchers want to know if their "normal" behavior is a result of "normal" brain activity, or if their brains process information in a non-typical way to compensate for any deficits.

Results from those tests are still being analyzed.

Most of the formerly autistic kids got long-term behavior treatment soon after diagnosis, in some cases for 30 or 40 hours weekly.

Many also have above-average IQs and had been diagnosed with relatively mild cases of autism. At age 2, many were within the normal range for motor development, able to walk, climb and hold a pencil.

Significant improvement suggesting recovery was evident by around age 7 in most cases, Fein said.

None of the children has shown any sign of relapse. But nearly three-fourths of the formerly autistic kids have had other disorders, including attention-deficit problems, tics and phobias; eight still are affected.

Jayne Lytel says Leo sometimes still gets upset easily but is much more flexible than before.